Regulators of the Actin Cytoskeleton Mediate Lethality in a Caenorhabditis elegans dhc-1 Mutant |
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Authors: | Aleksandra J Gil-Krzewska Erica Farber Edgar A Buttner Craig P Hunter |
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Institution: | Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 |
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Abstract: | Functional analysis of cytoplasmic dynein in Caenorhabditis elegans has revealed a wide range of cellular functions for this minus-end–directed motor protein. Dynein transports a variety of cargos to diverse cellular locations, and thus cargo selection and destination are likely regulated by accessory proteins. The microtubule-associated proteins LIS-1 and dynein interact, but the nature of this interaction remains poorly understood. Here we show that both LIS-1 and the dynein heavy-chain DHC-1 are required for integrity of the actin cytoskeleton in C. elegans. Although both dhc-1(or195ts) and lis-1 loss-of-function disrupt the actin cytoskeleton and produce embryonic lethality, a double mutant suppresses these defects. A targeted RNA interference screen revealed that knockdown of other actin regulators, including actin-capping protein genes and prefoldin subunit genes, suppresses dhc-1(or195ts)–induced lethality. We propose that release or relocation of the mutant dynein complex mediates this suppression of dhc-1(or195ts)--induced phenotypes. These results reveal an unexpected direct or indirect interaction between the actin cytoskeleton and dynein activity. |
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